Atorvastatin main mechanism of action is the inhibition of the activity of 3-hydroxy-3-metilglutarilkoenzim A – (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonic acid. This transformation is one of the early steps in the chain of cholesterol synthesis in the body. Inhibition of cholesterol synthesis atorvastatin leads to an increased reactivity of the LDL receptor anadrol steroid (low density lipoproteins) in the liver and extrahepatic tissues in. These receptors bind LDL particles and remove them from the plasma, resulting in a reduction of LDL cholesterol in the blood.
Antisclerosic effect atorvastatin is a consequence of the impact of the drug on the vessel walls and blood components. The drug inhibits the synthesis of isoprenoids, which are growth factors vascular inner lining of cells. Under the influence of atorvastatin improves endothelium-dependent vasodilation. Atorvastatin reduces cholesterol, LDL, apolipoprotein B, triglycerides. It causes an increase in HDL cholesterol (high-density dipoproteinov) and apolipoprotein A.
The action of the drug, usually develops after 2 weeks of treatment, and the maximum effect is achieved after four weeks.
Absorption – high. Time to maximum concentration – 2.1 h, the maximum concentration in women above 20%, AUC (area under curve) – below 10%, the maximum concentration in patients with alcoholic liver cirrhosis 16 times, AUC – 11 times higher than normal. Food somewhat reduces the rate and duration of absorption of the drug (25% and 9% respectively) but LDL cholesterol reduction similar to that in the application of atorvastatin without food. The concentration of atorvastatin in the evening application in lower than in the morning (approximately 30%). A linear relationship between dose and degree of absorption of the drug.
Bioavailability – 14% systemic bioavailability of inhibitory activity against HMG-CoA reductase – 30%. The low systemic bioavailability due to first-pass metabolism in the mucosa of the gastrointestinal tract, and the “first pass” through the liver.
The average volume of distribution – 381 liters, the connection with plasma proteins -. 98%
is metabolized primarily in the liver by the action of cytochrome P450 CYP3A4, CYP3A5 and CYP3A7 to form pharmacologically active metabolites (ortho- and para-hydroxylated derivatives, beta-oxidation products).
The inhibitory effect of the drug against HMG-CoA reductase inhibitor of approximately 70% determined by the activity of circulating metabolites.
Return with bile after hepatic and / or extrahepatic metabolism ( does not undergo pronounced enterohepatic recirculation).
The half-life -. 14 hours inhibitory activity against HMG-CoA reductase remains about 20-30 hours, due to the presence of active metabolites. Less than 2% of an oral dose is determined in the urine.
Not output during hemodialysis.
The primary hypercholesterolemia, mixed hyperlipidemia, heterozygous and homozygous familial hypercholesterolemia (as a supplement to the diet).
Hypersensitivity to any component of the drug, liver disease in the active stage (including chronic active hepatitis, chronic alcoholic hepatitis), increased activity “liver” enzymes (more than 3 times the upper limit of normal) of unknown origin, hepatic failure (severity A and B on the system Childe Pyuga), cirrhosis of any etiology, pregnancy, lactation, age 18 years (effectiveness and safety have been established).
Precautions : history of liver disease, severe electrolyte imbalance, endocrine and metabolic disorders, alcoholism, arterial hypotension, severe acute infection (sepsis), uncontrollable seizures, extensive surgery, trauma.
Dosing and Administration
Prior to treatment Liptonorm patient should be transferred to a diet providing a reduction in blood lipids, that must be observed during drug treatment.
Inside, take at any time of the day (but at the same time), regardless of the meal.
The recommended starting dose – 10 mg 1 time per day. Further dose picked individually depending on the cholesterol – LDL. Changing the dose should be at intervals of not less than 4 weeks. The maximum daily dose – 80 mg in 1 reception.
The primary (heterozygous hereditary and polygenic) hypercholesterolemia (type IIa) and mixed hyperlipidemia (type IIb)
Treatment started with the recommended initial dose, which increased after 4 weeks of therapy depending on the patient’s response. The maximum daily dose is 80 mg.
Homozygous Familial Hypercholesterolemia
The dose range is the same as for other types of hyperlipidemia. The initial dose is selected individually depending on the severity of the disease. Most patients with homozygous familial hypercholesterolemia optimum effect observed using the preparation in a daily dose of 80 mg (once).
In patients with renal impairment and elderly patients dose adjustment Liptonorm not required.
In patients with impaired hepatic function should be cautious due to the slowing of excretion of the drug. Clinical and laboratory parameters and the detection of significant lesions should be carefully monitored dose should be reduced or treatment should anadrol steroid be discontinued.
On the part of the central nervous system: in 2% of cases – insomnia, dizziness; in less than 2% of cases – headache, asthenic syndrome, malaise, drowsiness, nightmares, amnesia, paresthesia, peripheral neuropathy, amnesia, emotional lability, ataxia, paralysis of the facial nerve, hyperkinesis, depression, hypersensitivity, loss of consciousness. From the senses : amblyopia, tinnitus, dryness of the conjunctiva, disturbance of accommodation, eye hemorrhage, deafness, glaucoma, parosmiya, loss of taste, taste perversion. cardio-vascular system: in the case of more than 2% – pain in the chest; in less than 2% – palpitation, vasodilatation, migraine, postural hypotension, increased blood pressure, phlebitis, arrhythmia, angina. On the part of the hemopoietic system: anemia, lymphadenopathy, thrombocytopenia. The respiratory system: in more than 2% – bronchitis, rhinitis; in less than 2% – pneumonia, dyspnea, asthma, epistaxis. From the digestive system: in 2% of cases – nausea, heartburn, constipation or diarrhea, flatulence, gastralgia, abdominal pain, anorexia or increased appetite, dry mouth, regurgitation, dysphagia, vomiting, stomatitis, esophagitis, glossitis, erosive and ulcerative lesions of the oral mucosa, gastroenteritis, hepatitis, hepatic colic, cheilitis, duodenal ulcer, pancreatitis, cholestatic jaundice, abnormal liver function, rectal bleeding, melena, . bleeding gums, tenesmus From the musculoskeletal system: in more than 2% – arthritis; in less than 2% – spasms of the leg muscles, bursitis, tenosynovitis, myositis, myopathy, arthralgia, myalgia, rhabdomyolysis, torticollis, muscular hypertonicity, contracture of joints. With the genitourinary system: in more than 2% – urogenital infections, peripheral edema; in less than 2% – dysuria (including pollakiuria, nocturia, urinary incontinence or urinary retention, compelling urge to urinate), nephritis, hematuria, vaginal bleeding, nefrourolitiaz, metrorrhagia, epididymitis, decreased libido, impotence, abnormal ejaculation. For the skin: less than 2% – alopecia, dermatoxerasia, increased sweating, eczema, seborrhea, ecchymosis, petechiae. Allergic reaction: less than 2% of cases – itching, skin rash, contact dermatitis, rare – urticaria, angioedema, face edema, photosensitivity, anaphylaxis, erythema multiforme exudative, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome). Laboratory findings: less than 2% – hyperglycemia, hypoglycemia, increased serum creatine kinase, alkaline phosphatase, albuminuria, increased alanine aminotransferase (ALT) or asparaginaminotransferazy. Others: less than 2% – weight gain, gynecomastia, mammalgia, exacerbation of gout.
Treatment: No specific antidote. Symptomatic therapy. Take measures to maintain vital body functions and measures to prevent further absorption of the drug: gastric lavage, activated charcoal.Hemodialysis is ineffective.
If signs and the presence of risk factors for acute renal failure with rhabdomyolysis (a rare but serious side effect), the drug should be immediately abolished.
Since atorvastatin is largely bound to plasma proteins, hemodialysis is an ineffective way to remove this substance from the body.
Interaction with other drugs
When concomitant administration of cyclosporine, fibrates, erythromycin, clarithromycin, immunosuppressive, antifungal drugs (belonging to azoles) and nicotinamide concentration of atorvastatin in plasma (and the risk of myopathy) increases. Antacids reduce the concentration of 35% (effect on LDL cholesterol is not changed).
Simultaneous use of atorvastatin with protease inhibitors, known as inhibitors of the cytochrome P450 CYP3A4, accompanied by an increase atorvastatin plasma concentration.
When using digoxin in combination with atorvastatin 80 mg / day concentration of digoxin increased by about 20%.
Increases concentration of 20% (in the appointment of atorvastatin at a dose of 80 mg / day) oral contraceptives containing norethindrone and ethinyl estradiol.
Lipid-lowering effect of combination with colestipol than that for each drug individually.
at simultaneous reception with warfarin in the first days decreased prothrombin time, but after 15 days, the figure is normalized. In this regard, patients taking warfarin atorvastatin should be more than usual to monitor the prothrombin time.
Juice Grapefruit Use for atorvastatin may increase the plasma concentration of the drug. Therefore, patients taking the drug should avoid drinking this juice.
Violation of liver function
use of inhibitors of HMG-CoA reductase inhibitor to lower lipid levels in the blood can lead to changes in biochemical parameters that reflect the function of the liver.
Liver function should be monitored before treatment and after 6 weeks, 12 weeks after the start of Liptonorm and after each dose escalation and periodically, such as every six months. Changes in the activity of liver enzymes usually occurs during the first three months after initiation of Liptonorm. Patients in whom there is an increase in transaminase levels should be controlled to the level of enzymes return to normal. In that case, if the values of alanine aminotransferase (ALT) or asparaginaminotransferazy (AST) is more than 3 times higher than the level of the upper allowable limit, it is advisable to reduce the dose Liptonorm or discontinue treatment.
Patients with diffuse myalgia, lethargy or weakness of the muscles and / or a significant increase in CPK are risk group for the development of myopathy (defined as muscle pain with a concomitant increase in CK levels more than 10 times compared to the upper limit of normal).
When appointment of combination therapy Liptonorm with cyclosporin derivatives fiber acid, erythromycin, clarithromycin, immunosuppressive, and anti-fungal drugs azole structure and causes a decrease in the level of lipid doses of niacin, it is necessary to compare the potential benefits and the degree of risk for a given treatment and to monitor patients who show signs or symptoms of muscle pain, weakness, or weakness, particularly during the first few months of treatment and at higher doses of either drug.
Liptonorm Treatment should be suspended or terminated at the serious condition of the development, which may be a consequence of myopathy, as well as the presence of risk factors for the development of acute renal failure due to rhabdomyolysis (eg, acute severe infection, hypotension, major surgery, trauma, severe metabolic and endocrine disorders, and disorders of electrolyte balance).
In women of reproductive age who are not using reliable contraception, Liptonorm use is not recommended. If anadrol steroid the patient plans pregnancy, she should stop taking Liptonorm at least one month before the planned pregnancy.
The patient should immediately consult a doctor if unexplained pain or weakness in muscles, particularly if accompanied by malaise and fever. anastrozole steroid